OBJECTIVE To investigate the risk factors for sodium valproate （VPA）-induced hyperammonemia in neurocritical patients， and to construct a risk prediction model. METHODS Clinical data were retrospectively collected from 172 neurocritical patients who received VPA treatment in the Department of Critical Care Medicine， the Fourth Affiliated Hospital of Soochow University from January 2022 to June 2025. Patients were divided into the hyperammonemia group （73 cases） and the normal group （99 cases） based on their blood ammonia levels. Univariate analysis and LASSO regression analysis were used to screen for predictive variables. Independent factors were identified through multivariate Logistic regression analysis， and a nomogram was constructed accordingly. The performance of the model was evaluated using receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis （DCA）. RESULTS Combination of univariate analysis and LASSO regression analysis screened out seven predictive variables： body mass index （BMI）≥24.0 kg/m 2 ， concomitant use of benzodiazepines， VPA blood concentration， hemoglobin， serum urea， average daily VPA dose， and albumin. Multivariate Logistic regression analysis showed that concomitant use of benzodiazepines， BMI≥24.0 kg/m 2 ， VPA blood concentration， albumin and serum urea level （with odds ratios of 1.615， 1.538， 1.623， 1.942 and 0.637， respectively； 95% confidence intervals of 1.128-2.359， 1.059-2.251， 1.112-2.431， 1.106-3.598 and 0.402-0.980， respectively） were all significantly associated with VPA-induced hyperammonemia in neurocritical patients （ P ＜0.05）. The nomogram prediction model constructed based on these variables was evaluated， showing that the area under the ROC curve was 0.810 for the test set and 0.844 for the validation set. The calibration curves closely approximated t he actual curves， and the application of this model could improve the clinical net benefit. CONCLUSIONS Concomitant use of benzodiazepines， BMI≥24.0 kg/m 2 ， high VPA blood concentration and high albumin level are independent risk factors for VPA-induced hyperammonemia in neurocritical patients， while high serum urea level is an independent protective factor. The risk prediction model constructed based on these factors exhibits good discrimination， consistency， and clinical applicability， making it applicable for predicting the risk of VPA-induced hyperammonemia in neurocritical patients.

Breast cancer patients in China tend to be diagnosed at a younger age, making fertility issues a significant clinical and societal challenge. Current evidence indicates that the fertility rate among breast cancer survivors is substantially lower than that of the general population of the same age. Both the disease itself and anti-tumor treatments-including chemotherapy, radiotherapy, endocrine therapy, targeted therapy, and immunotherapy-can adversely affect female fertility. Therefore, fertility considera-tions should be integrated into the comprehensive management of breast cancer from the time of diagnosis. Several guidelines and consensus statements have been established to direct fertility management in these patients. Clinical practice has achieved some success in fertility preservation through pharmacological, surgical, and assisted reproductive technologies, which help mitigate treatment-related damage to fertility. Nevertheless, further progress relies on multidisciplinary collaboration, particularly in addressing the ethical and legal aspects of fertility preservation. Recent advances in research on hereditary breast cancer, risk assessment, and preimplantation genetic testing for polygenic diseases offer new perspectives and directions for fertility management in breast cancer patients. This review systematically summarizes the current fertility status, existing management strategies, and cutting-edge research on healthy reproduction in breast cancer patients, with the aim of supporting the standardization of fertility management protocols.

Ovarian tissue cryopreservation and transplantation is currently the only feasible method for preserving both fertility and ovarian endocrine function in prepubertal female patients. It is indicated for those requiring gonadotoxic therapies such as chemo-therapy, radiotherapy, or bone marrow transplantation for malignant diseases, as well as for non-malignant diseases, including immunologic, metabolic, and hematologic benign diseases requiring bone marrow transplantation, and other populations at high risk of premature ovarian insufficiency. The procedure involves laparoscopic retrieval of ovarian tissue, typically via unilateral oophorectomy in young patients, followed by slow-programmed cryopreservation. When the primary disease is cured and fertility or hormonal function restoration is desired, the tissue is thawed and transplanted, most commonly to an orthotopic site. For patients at high risk of ovarian malignancy involvement, pre-transplantation assessment of minimal residual disease in the ovarian cortex is performed using histo-pathology and molecular biology techniques. Globally, while ovarian tissue cryopreservation and transplantation has led to over 300 live births, the majority result from tissue cryopreserved after puberty. Successful restoration of puberty and subsequent live births following transplantation of tissue frozen before puberty, although demonstrated in reported cases, remain less common. Therefore, this review systematically summarizes recent advances in the indications, current application status, timing and strategies of ovarian tissue cryopreservation and transplantation, risk assessment of tumor cell reintroduction, and clinical outcomes in prepubertal patients. It also discusses the potential value and current challenges of combining this approach with invitro oocyte maturation techniques, ainming to provide practical references for clinical practice.

Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE^-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.

ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹-¹ and Hcy>15 μmol·L⁻¹ was 1.532 times (95%CI: 1.017‒2.309 times, P=0.041) and 1.738 times (95%CI: 1.119‒2.699 times, P=0.014) higher respectively, compared to T2DM patients with Hcy≤10 μmol·L⁻¹. T2DM patients with TyG>9.074 had 1.396 times higher risk of stroke (95%CI: 1.091‒1.787, P=0.008) compared to those with TyG≤9.074. The study found that urea and α1-antitrypsin (α1-AT) were independent risk factors for the incidence of stroke in T2DM patients. For every unit increase in urea andα1-AT, the risk of stroke in T2DM patients increased by 233.6% (HR=3.336, 95%CI: 1.588‒7.009, P=0.001) and 11.3% (HR=1.113, 95%CI: 1.028‒1.205, P=0.008), respectively. Cumulative risk curves showed that Hcy>10 μmol·L⁻¹ and TyG>9.074 accelerated the time to stroke occurrence in T2DM patients. ConclusionElevated levels of Hcy>10 μmol·L⁻¹ and a higher TyG index are risk factors for stroke in T2DM patients. Effective interventions for Hcy and TyG should be conducted for diabetic patients to reduce the incidence of stroke.

Objective To explore the role of cysteine aspartic protease-8(Caspase-8)/gasdermin E(GSDME)pathway in the regulation of macrophage pyroptosis in myocardial infarction(MI)rat model and its possible mechanism.Methods Thirty rats were randomly divided into sham operation group,MI group and Caspase-8 inhibition(Z-IETD-FMK)group,with 10 rats in each group.The cultured rat macrophages RMa-bm were divided into control group,hypoxia group and Z-IETD-FMK group.The pathological changes of myocardial tissue were detected by H&E staining.Masson staining was used to detect myocardial fibrosis.The protein and mRNA levels of Caspase-8 and GSDME in myocardial tissue and Caspase-8,GSDME,NLR family Pyrin domain protein 3(NLRP3),apoptosis-related speck-like protein(ASC)and Caspase-1 in macrophages were detected by RT-qPCR and Western blotting.The levels of IL-1β and IL-18 in macrophages were detected by ELISA.TUNEL staining was used to detect apoptosis of cardiomyocytes and macrophages.Results Compared with the sham operation group,myocardial tissue of rats in MI group was broken and disturbed,inflammatory cell infiltration,a large amount of collagen fiber deposition in the gap,cell apoptosis increased and the expression of Caspase-8,GSDME protein and mRNA in myocardial tissue increased,the differences were statistically significant(t=16.19,27.60;21.18,23.73,all P<0.05).Compared with MI group,Z-IETD-FMK group improved myocardial structural damage,reduced inflammatory cells and collagen deposition,cell apoptosis decreased and decreased Caspase-8,GSDME protein and mRNA expressions in myocardial tissue,with statistical significance(t=20.34,14.56;11.97,24.46,all P<0.05).Compared with the control group,the apoptosis of macrophages in hypoxia group was increased,and the protein and mRNA expressions of Caspase-8,GSDME,NLRP3,ASC,Caspase-1 in macrophages were increased(tprotein=17.53～120.90,tmRNA=18.42～60.30),the contents of IL-1β and IL-18 in macrophages were increased(t=25.88,45.74),and the differences were staistically significant(all P<0.05).Compared with the hypoxia group,the apoptosis of macrophages in Z-IETD-FMK group was decreased,and the protein and mRNA expressions of Caspase-8,GSDME,NLRP3,ASC,Caspase-1 in macrophages were decreased(tprotein=17.08～35.08,tmRNA=11.21～47.96),IL-1β and IL-18 content decreased(t=27.38,25.82),and the differences were staistically significant(all P<0.05),respectively.Conclusion Down-regulating Caspase-8/GSDME pathway can improve myocardial injury and hypoxic macrophage scorch death in MI rats.

Objective:To evaluate the perceived level of home exercise behavior in elderly patients with ovarian cancer and analyze its influencing factors, so as to promote home exercise behavior of patients and improve the quality of life.Methods:A total of 227 elderly patients with ovarian cancer from January 1, 2021 to October 1, 2023 in the First Affiliated Hospital, School of Medicine, Zhejiang University were selected by convenience sampling method. A cross-sectional survey was conducted by General Information Questionnaire, Exercise Benefits/Barriers Scale (EBBS), Social Support Rating Scale (SSRS), General Self-efficacy Scale (GSES) and Brief Fatigue Inventory (BFI). The influencing factors on the perceived level of home exercise behavior in elderly patients with ovarian cancer were analyzed.Results:There were 227 elderly female patients with ovarian cancer, including 151 patients aged<70 years old and 76 patients aged ≥70 years old. The scores of EBBS, SSRS, GSES, BFI were (123.37±11.02), (37.68±7.44), (29.35±6.54), (5.82±2.01) points. The perception of exercise behavior was positively correlated with general self-efficacy and social support ( r=0.752, 0.901, both P<0.01), was negatively correlated with cancer-related fatigue ( r=-0.198, P<0.01). The results showed that general self-efficacy, social support, age≥70 years old, no spouse, not being informed of the benefits of exercise,fatigue due to moderate and severe cancer, duration of disease ≥12 months were the influencing factors ( t values were -4.56 - 4.46, all P<0.05). Conclusions:Elderly patients with ovarian cancer need to improve their perception level of home exercise behavior. In the formulation of home exercise behavior for elderly patients with ovarian cancer, education and cognition on the perceived benefits of home exercise behavior should be strengthened, and patients′ physical and mental status should be evaluated before exercise to actively reduce cancer-related fatigue. At the same time, the combination of family support can improve the perceived level of exercise behavior of elderly patients with ovarian cancer at home, so as to promote home exercise behavior of patients.

Objective To explore the clinical characteristics of the patients with follicular cysts and menstrual disorders.Methods A total of 178 women with follicular cysts complicated by menstrual disorders were recruited,who were aged 23-53(38.62±6.35)years and came to the Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital between August 2022 and July 2024.The participants were divided into three groups according to the age,with 27 women in the age group of 21-30 years(Group 1),77 in the age group of 31-40 years(Group 2),and 74 in the age group of>40 years(Group 3).The age and menstruation of these patients were collected,the body height,weight,follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),progesterone(Po),total testosterone(TT),prolactin(PRL),anti-müllerian hormone(AMH)and thyroid function[blood routine and blood clotting for patients with abnormal uterine bleeding(AUB)]were measured,and the diameter of ovarian cyst and the thickness of endometrium were examined.The clinical characteristics of the patients with follicular cysts complicated by menstrual disorders were described and compared with each other among the three age groups.Results ① Among 178 patients,61(34.3%)patients presented with complaints of cessation of regular menstruation or amenorrhea and 117(65.7%)with complaints of AUB.Out of 178 patients,13(7.3%)patients developed anemia due to AUB,and all the patients were treated with medication.② Follicular cysts disappeared in 1 month for 124(69.7%)patients,disappeared in 2 months for 176(98.9%)patients,and disappeared in 3 months for 178(100%)patients.A total of 177(99.4%)patients had follicular cysts with a diameter less than 5 cm,and only 1(0.6%)patient had follicular cysts with a diameter≥5 cm.③ The overall prevalence of diminished ovarian reserve(DOR)in patients with follicular cysts complicated by menstrual disorders was 82.0%,and the prevalence of DOR was 70.2%for the patients under 40 years old.The prevalence of DOR in three age groups was 37.0%(10/27),81.8%(63/77),and 98.6%(73/74),respectively.The prevalence of DOR gradually increased with age.④ The median AMH values for Group 1,Group 2,and Group 3 were 1.55,0.51,and 0.15 ng/mL,respectively.The FSH level in Group 3 was significantly higher than that in Groups 1 and 2(adjusted P<0.05),while the AMH level was significantly lower than that in Groups 1 and 2(adjusted P<0.05).The AMH level in Group 2 was lower than that in Group 1(adjusted P<0.05).Conclusion Patients with follicular cysts complicated by menstrual disorders are recommended to receive medication treatment,rather than just expecting treatment.The prevalence of DOR in patients with follicular cysts complicated by menstrual disorders is significantly higher than that in normal women,even in women younger than 40 years old.Therefore,it is essential to evaluate the ovarian reserve of these patients while treating menstrual disorders,particularly for young women with fertility needs.

Objective To evaluate the impact of slow-freezing process on human ovarian tissue with the standard cryopreservation-thawing protocol of Fertility Protection Center of Beijing Obstetrics and Gynecology Hospital,Capital Medical University.Methods Ovarian tissues of 12 patients were divided into fresh ovarian tissue group(fresh group)and freezing-thawing ovarian tissue group(F-T group).The freezing-thawing protocol was the standard protocol in our center.The number and activity of follicle were examined with Hematoxylin-eosin(HE)staining and calcein-AM(calcein acetoxymethylester)staining,and the proliferation and apoptosis was evaluated with the immunohistochemical staining of Ki-67 and caspase-3.The expressions of apoptosis-related proteins such as caspase-3,bax and FasL between the two groups were compared with Western blotting.Results There were no statistically significant differences in follicle counting and follicle activity in ovarian tissues pre-and post-freezing-thawing(P>0.05),and the positive rate of Ki-67 in ovarian tissues after freezing-thawing was significantly lower than that in fresh ovarian tissues(P<0.05),and there was no statistically significant difference in the positive rate of caspase-3 between the two groups(P>0.05).The expression of caspase-3 protein in ovarian tissues after freezing-thawing was significantly higher than that in fresh ovarian tissues(P<0.05),while the expressions of other apoptosis-related proteins such as bax and FasL were not significantly different(P>0.05).Conclusion The standard cryopreservation-thawing regimen in our center can effectively maintain the follicle number,morphology,and activity in ovarian tissues.After freezing and thawing,the cell proliferation level is decreased.The expression of apoptosis-related proteins such as bax and FasL are not increased,and the expression of caspase-3 is relatively increased.These results suggest our freezing-thawing regimen is good for human ovarian tissue.

Female infertility is recognized as a global public health issue by the World Health Organization.Female fertility remodeling includes ovarian function reconstruction and uterus/endometrium reconstruction,etc.It is emerging as a hot technology since it is ready to prepare autologous platelet-rich concentrate and it is safer and more acceptable in autologous application.It plays an important role in regenerative medicine,and it is currently widely applied in maxillofacial and plastic surgery,dermatology and other clinical practices.This article mainly reviews the progresses of the application of autologous platelet-rich concentrate in female fertility remodeling.